The ‘Brain Chemist’

John Lowry, Prof of Chemistry at NUIM, had planned to become an astrophysicist like his hero Carl Sagan, but he became more interested in the chemistry of the human brain.

Depression, Alzheimer’s, and schizophrenia are all diseases of the brain, and can destroy the lives of sufferers and their families. Drug therapies exist – though not for Alzheimer’s – but these are far from perfect. The drugs work for some, not for others, while side-effects can be severe. A huge road-block preventing the development of better drugs for brain diseases is the fact that little is known about the chemistry of the brain in general or the chemistry of the diseased brain in particular. For example, little is known about what is happening – chemically – in the brain of a person with schizophrenia as he walks around experiencing symptoms. This ‘knowledge gap’ is something that John Lowry, a softly spoken, talented, and far-sighted scientist is addressing at his laboratory at NUIM.

The first step to developing better drugs for brain disease, said John, to develop a far better understanding of what is happening chemically in the brain, and in the diseased brain, to lay the groundwork for the development of new, and much better, treatments. This is the area that John is working in, and his lab is one of the few in Europe, and even worldwide that is capable of analyzing brain chemical concentrations in ‘real time’. To do this it is essential to work with animals, typically rats, to get true ‘in vivo’ readings.

PERSONABLE

John is the type of scientist that would give Irish scientists a good name. He is open, personable, accommodating, and understanding of the importance of the media and communicating science to the public. He understands that TV in particular has the power to ignite an interest in science, in young minds. He is a superb researcher, certainly one of Ireland’s best, and works in an area that has the potential to improve real people’s lives beyond measure. His work is recognized internationally, and his lab is well-funded and resourced. Some in this position might be arrogant, or aloof. John is the polar opposite.

Perhaps this modesty stems in part from his origins, born into what he describes as a ‘working class’ family in Tullamore. His Dad had planned that young John would be signed up sometime shortly after his Intermediate Certificate (now called the Junior Cert) to become a plumber’s apprentice. His father meant well, of course, and wanted the best for his son, but John had other ideas. He wanted to be a scientist, and that was that. His Dad didn’t argue the point, and his education continued to Leaving Cert and to college.

PASSION

From 6th class in primary school John wanted to be an astrophysicist, studying the great mysteries of the Universe. The inspiration for this ambition came from watching the US TV show, Cosmos, presented by Carl Sagan, the great astronomer and communicator. The show was watched by an estimated 500 million viewers worldwide, and John, like many others, was held spellbound by the skills of this brilliant populariser of science. He also watched repeat showings of BBC’s Horizon show on RTE on Saturday mornings.

But, it was Sagan, more than anyone that lit the fire and passion for science in young John. He devoured any books he could find written by Sagan, including Broca’s Brain: Reflections on the Romance of Science and Dragon’s of Eden: Speculations on the Evolution of Human Intelligence and pestered the local library to order in more. The brilliance of Sagan, and people like him, such as David Attenborough, says John, are crucial, to generate interest in a subject among young people. It has to be the right person, he says, and TV can provide students with access to these brilliant, gifted communicators.

So, John was already fired with a passion for science by the time he entered secondary school at the Christian Brothers School in Tullamore. After the Intermediate Cert, where he took science as a single subject, same as today, he decided he wanted to take all three main science subjects for leaving certificate, but he ran into opposition. The school authorities felt that no-one should take on the 3 science subjects as it would be too much, and John was pressurized into dropping physics in favour of economics. That decision stood for a week, after which John went back and took physics, supported by the Principal – his athletics coach and a friend. He went on to prove the doubters wrong, and did very well in his leaving in all three science subjects, something he puts down to his love of science.

OPTIONS

After the Leaving, it was time to consider where to go to university. By this time, John, while still interested in astrophysics, was not 100 per cent sure what branch of science that he would ultimately focus on. Wisely, as it turned out, he decided to go to UCD where he felt the ‘Omnibus’ degree on offer., which was broader than what some other universities were offering, would provide him the opportunity to consider all his options.

At UCD, he took physics, chemistry, biology, maths and computers in his first year. He dropped physics after first year, something he would have never anticipated, and kept chemistry, biology and maths in second year. In third year he chose, chemistry and maths Already it was clear he was gravitating towards a career in chemistry rather than physics or astrophysics as he might have expected, given his early fascination with Sagan’s work.

John got his degree and was certain then that he wanted to go on, and do more research. He loved the idea of working in the lab, and discovering new things, and began looking around for interesting post-graduate opportunities. He went to listen to a few lectures on the subject of neuro-chemistry by Robert O’Neill, an Irish scientist that had come back to UCD after a period in Oxford University. “He sold it to me,” John recalls. That was that.

RESEARCH

John’s problem-solving skills were needed immediately when he went to Robert’s lab. Today’s PhD candidates expect, from day one, to have access to equipment and start gathering data when they enter a lab. In the late 1980s and early 1990s things were very different. John recalls that he spent the first six months of his PhD working hard, just setting up his equipment, and writing software so that everything would work together, before he collected any data. If he didn’t do this then his PhD wouldn’t happen, he said.

The focus of his PhD was to develop a sensor that could gather information on glucose levels in the brain, in ‘real time’. This was something very new, and potentially very important. He applied for a Marie Curie fellowship, a European Commission funded scheme to encourage post-graduate students to work in a laboratory abroad, and bring the knowledge they gain back to their host country later. It provides the funds for the student, so the university that agree to take the student, do not need to financially support him.

John wanted to go to Oxford University. He wrote an application and was successful, and joined the lab of the “phenomenally inspirational” Dr Marianne Fillenz. For a while, Dr Fillenz didn’t know what to do with John. He said he had developed a method to do ‘real time’ measurements of glucose in the brain, but the Oxford lab had their own methods. After he was trained up so that he could do experiments, John started to collect data. He sat down with Dr Fillenz to analyze the data, and she then realized that what John was doing was a huge step forward, as it provided ‘real time’ data on brain chemical levels.

FUTURE

John does believe that better drugs for brain diseases will be developed in coming decades, but that issues need to be addressed in the pharmaceutical industry for that to happen. At the moment, the drug development business model is under threat, as even ‘big pharma’ giants cannot sustain losses, should a drug fail in clinical trials. If a drug fails at a late stage it could mean losses of well over €500,000, which is too big a risk.

What will happen in future years, he believes, is that big pharma will only want to develop drugs that have excellent pre-clinical data, so that the risk of a drug failing at an advanced stage of the clinical trial process – where drugs are tested with humans – is reduced. It is likely that the pre-clinical drug development work will be done by smaller biotech companies, and this represents an opportunity for future ‘biotech’ entrepreneurs.

John himself has got involved in the commercial side of things, with the setting up of Blue Box Sensors, a spin-out from NUIM, based on his research work, in 2009. The company declares on its website: “We produce implantable micro sensors that allow long-term measurements of NO, O2 or glucose in awake and freely moving animals.”

ADVICE

His advice for anyone that is considering doing science in college is, firstly, to be sure that there is an interest, and ideally, a passion for science. If that is in place, then science is a good career option, and can help students get a job, or to get interviews, even in the current climate. A post-grad degree can move someone up even a notch higher, he says.

In hindsight, he says, he might well have signed up to do astrophysics, had there been an astrophysics only degree option available in 1984 when he entered college. In light of what direction his career later took that might well have been a mistake, he says. For this reason, he advises students today to be careful about choosing highly specialized single subject degrees. If an 18-year old knows exactly what he wants to do, then fine, but if a person has a general love of science, but is not sure what he likes best, then a broader degree is the way to go. That way a student can ‘test the waters’ and specialize later.

Back in 1984, entering college, John couldn’t have predicted his career path to date. I started out wanting to be an astrophysicist looking at the Universe on a large scale, and ended up studying a smaller Universe, said John. “Because the complexities of the brain, I think, certainly equal the complexities of the Universe. It is a Universe in its own right.”